Presentation on theme: "Metabolic Bone Disease Bone Study Day, 28th September 2012"— Presentation transcript:
1Metabolic Bone Disease Bone Study Day, 28th September 2012 of PrematurityZulf MughalConsultant in Paediatric Bone DisordersDepartment of Paediatric EndocriologyRoyal Manchester Children's HospitalManchesterM13 0JHBone Study Day, 28th September 2012
2Metabolic Bone Disease of Prematurity AetiologyFracturesAssessmentPrevention
3Aetiology of Metabolic Bone Disease of Prematurity
4Aetiology of Metabolic Bone Disease of Prematurity Preterm birth - bulk of the mineral transfer from mother to baby occurs in last third of pregnancyInadequate supply of minerals in diet after birthIncreased loss of minerals from infant’s bones after birth:Stoppage of movementsLoss of oestrogenMBP is a well known complication of prematurity. Risk inversly related to BW and gestational age and directly with postnatal morbidity (CLD, TPN & delay in enteral feeding).Usually diagnosed at 2 to 4 months postnatal age:Osteopenia on a radiographLow BMD for corrected gestation.Abnormal biochemistry (low Pi & high ALP)FracturesCause multifactorial:Missed out on 3rd trimester package of mineralsDecreased availability of minerals postnatallyFeeds deficient in Ca & PInability to tolerate/absorb enteral feeds, e.g. due to NEC or short bowel syndromeLow Ca & P in TPN solutionSkeletal demineralisation, especially during the rapid postnatal growth phaseDrugs – Frusemide & corticosteroidsImobilisationNo evidence that vitamin D def. plays an important part unless mother is deficient. Or the child has liver disease.
5Aetiology of Metabolic Bone Disease of Prematurity Increased risk of MBP<1000 gm birth weight (ELBW)Prolonged TPN (>2 weeks)MedicationsCorticosteroidsFrusemideInadequate bone-nutrient intakeIncreased urinary Phosphate wastage
6Metabolic Bone Disease of Prematurity Humerus of 26 week gestation, preterm infant at birth (A) and 6 weeks later (B)Marked thinning of the cortexOsteopaeniaPoznanski et al. Radiology 1980
7Post-natal Changes in Bone Mineralisation Greer FR J Peds 1988
8Aetiology of Metabolic Bone Disease of Prematurity Longitudinal study in 85 preterm infants < 1.5 kgMeasured Speed of Sound (SOS m/s)Tibial length (measured by knemometry)SOS measurements was 27 weeks (23 to 37.6) and 877 grams (418 to 1495), respectively. Measurements were performed weekly; median period of 4 weeks (1 to 16).The data for knee heel length and tibial SOS over time in 85 babies (Figs.5&6) and preliminary data for markers of bone turnover in a subset of 24 babies (Figs.9&10), was analysed by a ‘within subjects’ correlation.
9A longitudinal study of tibial speed of sound and lower limb length in preterm infants Knee heel length (mm) over timeTibial SOS (m/s)Knee heel length (mm)r=0.96;p<0.001r=-0.28; p<0.033r = 0.96; p < 0.001Postnatal age (weeks)
10A longitudinal study of tibial speed of sound and lower limb length in preterm infants r=0.96;p<0.001r=-0.28; p<0.033
13Fracture Incidence in Low Birth Weight Infants 78 VLBW infants; 23 to 36week gestationHuman milk or formula fed69% had evidence of fractureMost common sites:RibsRadius ± ulnaFemurKoo WWK et al J Pediar Orthop 9:326, 1989
15Subjects 106 infants identified 72 included in the study Birth weight range gGestation range weeksAll radiographs reviewed by Dr Neville Wright (n=1762)20% radiographs reviewed by Dr Sarah Russell (n=558)FIGURE 10 AP radiograph of a newborn with campomelic dysplasia. Of note is the absence of vertebral pedicles (small arrowheads) in the thoracic spine (present in the lumbar spine) and 11 pairs of ribs. A nearly diagnostic and uniform feature is the hypoplastic scapulae (large arrowhead). Not seen here but often present are cervical kyphosis and cervical or thoracic scoliosis.FIGURE 17 (A) Ultrasound performed at 23.5 weeks due to suspicion of skeletal dysplasia. Mildly shortened femurs were noted at 12 weeks and repeat ultrasound at 19 weeks showed micromelia, small thorax, and marked midface hypoplasia. Based on the findings, the parents were counseled that the fetus had a lethal condition and that thanatophoric dysplasia (TD) was the likely diagnosis. This view of the fetus shows the narrow chest diameter compared to the abdomen. After termination of pregnancy, the diagnosis of type 1 was confirmed by radiographs and molecular analysis. (B) Radiograph of the fetus with TDI. This diagnosis was subsequently confirmed by molecular analysis, which showed the C742T mutation in the FGFR3 gene (typical of TDI). The radiographic findings are severely shortened limbs with trident positioning of the fingers and bowed femurs. In the thorax, there are H-shaped platyspondyly and short ribs. TD is broadly classified into two types. TD1 causes bent/angulated femurs. TD2 is associated with cloverleaf skull caused by multiple craniosynostoses and relatively straight femurs.Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi: /adc
16Number and Sites of rib fractures Results 15 infants (7%) had Rib #sNONE had posterior shaft #sAll infants with rib #s died3 infants had non Rib #sNumber and Sites of rib fracturesDenise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi: /adc
17Results 2 Mann Whitney U Test: Infants with Rib #s vs those with No #s Highest Alkaline Phosphatase (ALP) p = 0.08Birth weight p = 0.52Gestation p = 0.22Corticosteroids p = 0.07Frusemide p = 0.03 *Chronic Lung Disease p = 0.36Chest Drains p = 0.57Total Parentral Nutrition (TPN) p = 0.08FIGURE 18 A fetus assessed for short limbs at 22 weeks of gestation. Of note, the head was relatively large and on profile had features of achondroplasia. Most noticeable was the prominent forehead and the depressed nasal bridge. (B) On inspection of the extremities, the diagnosis of achondroplasia was supported by the finding of trident hand. The diagnosis was confirmed postnatally.Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi: /adc
18Summary All infants with Rib #s died None had posterior Rib # Only 7% of ELBW infants had radiologically apparent Rib #sAll infants with Rib #s diedNone had posterior Rib #No temporal relationship between CPR & Rib #sInfants with Rib #s more likely to be treated with Frusemide.Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi: /adc
20Assessment of MBDP Clinical: Research: Serum Calcium and Phosphate concentrationsSerum Alkaline Phosphatase activitySerum PTHRadiographs – when necessaryResearch:Biochemical markers of bone turnoverBone densitometryQuantitative ultrasound
21Recommended Intake for Premature Infants (per Kg/day) Energy KcalCalcium mgPhosphorus mgVitamin D IUNeeds met by fortification of mother’s milkor premature infant formula
23Could a program of daily physical activity with adequate dietary intake improve bone mineralisation in premature infants?
24Distal 1/3 Radius Bone Mineral Change by pDXA Prevention of MBDPIdeal postnatal rate of mineralisation not known. Ca 120 to 150 mg/kg & P ~75 mg/kg.VARIABLES: absorption, losses and retention.Breast-milk with a fortifier or high mineral preterm formula milk. Duration ?. Most people would use high formula until postmenstural term age or at lease when body weight is >2kg weight.WEEKLY MEASUREMENT OF Ca, P & ALP.Mineral supplements until radiographic healing of bonesVitamin D ? 400 or 880 i.u?No evidence that Rx with Calcitriol or alphacalcidiol is any better.Biochemical aims:Ca with the normal limitsP >4 mg/dlIf ALP is > 5 times the upper limits then radiograph of the hand and rist is indicated.CONVERSATION:Calcium 1 mmol = 40 mgPhosphate 1 mmol = 31 mgMoyer-Mileur et al, J Peds 1995